Lysine-63-linked ubiquitination is required for endolysosomal degradation of class I molecules

MHC class I molecules display peptides from endogenous and viral proteins for immunosurveillance by cytotoxic T lymphocytes (CTL). The importance of the class I pathway is emphasised by the remarkable strategies employed by different viruses to downregulate surface class I and avoid CTL recognition....

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:The EMBO journal 2006-04, Vol.25 (8), p.1635-1645
Hauptverfasser: Duncan, Lidia M, Piper, Siân, Dodd, Roger B, Saville, Mark K, Sanderson, Chris M, Luzio, J Paul, Lehner, Paul J
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext bestellen
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:MHC class I molecules display peptides from endogenous and viral proteins for immunosurveillance by cytotoxic T lymphocytes (CTL). The importance of the class I pathway is emphasised by the remarkable strategies employed by different viruses to downregulate surface class I and avoid CTL recognition. The K3 gene product from Kaposi's sarcoma‐associated herpesvirus (KSHV) is a viral ubiquitin E3 ligase which ubiquitinates and degrades cell surface MHC class I molecules. We now show that modification of K3‐associated class I by lysine‐63‐linked polyubiquitin chains is necessary for their efficient endocytosis and endolysosomal degradation and present three lines of evidence that monoubiquitination of class I molecules provides an inefficient internalisation signal. This lysine‐63‐linked polyubiquitination requires both UbcH5b/c and Ubc13‐conjugating enzymes for initiating mono‐ and subsequent polyubiquitination of class I, and the clathrin‐dependent internalisation is mediated by the epsin endocytic adaptor. Our results explain how lysine‐63‐linked polyubiquitination leads to degradation by an endolysosomal pathway and demonstrate a novel mechanism for endocytosis and endolysosomal degradation of class I, which may be applicable to other receptors.
ISSN:0261-4189
1460-2075
DOI:10.1038/sj.emboj.7601056